Homoharringtonine promotes BCR‑ABL degradation through the p62‑mediated autophagy pathway.

ABSTRACT: Drug resistance to tyrosine kinase inhibitors (TKIs) is currently a clinical problem in patients with chronic myelogenous leukemia (CML). Homoharringtonine (HHT) is an approved treatment for adult patients with chronic‑ or accelerated‑phase CML who are resistant to TKIs and other therapies; however, the underlying mechanisms remain unclear. In the present study, HHT treatment demonstrated induction of apoptosis in imatinib‑resistant K562G cells by using MTS assay and western blotting, and BCR‑ABL protein was reduced. CHX chase assay revealed that HHT induced degradation of the BCR‑ABL protein, which could be reversed by autophagy lysosome inhibitors Baf‑A1 and CQ. Next, HHT treatment confirmed the induction of autophagy in K562G cells, and silencing the key autophagic proteins ATG5 and Bec

SUBMITTER: Li S 

PROVIDER: S-EPMC6908937 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature